The present invention relates to sulfone compounds that are useful intermediate compounds for the production of pharmaceuticals, feed additives or food additives such as retinol, and production methods for producing the same, and a process for the production of retinol using the same.
There has been disclosed a process for producing retinol by reacting a sulfone of formula (6) shown below with a C10 aldehyde compound derived from linalool by a plurality of steps to obtain a C20 hydroxy sulfone compound, and derivatizing the same by a plurality of steps (U.S. Pat. No. 4,825,006). However, there is a demand for the development of a further improved industrial production process for producing retinol.
According to the present invention, retinol can be readily obtained by using novel sulfone compounds and a readily available C5 allyl halide compound.
The present invention provides
1. a disulfone compound of formula (1): 
xe2x80x83wherein Ar denotes a substituted or unsubstituted aryl group, R1 denotes a hydrogen atom or a protective group of a hydroxyl group and the wavy line means that the disulfone compound is an E or Z geometrical isomer or a mixture thereof;
2. a process for producing the disulfone compound of formula (1) as defined above, which comprises reacting an allylsulfone of formula (2): 
xe2x80x83wherein Ar and the wavy line have the same meanings as defined in connection with formula (1) above, with an allyl halide compound of formula (3): 
xe2x80x83wherein X denotes a halogen atom, R denotes a protective group of a hydroxyl group and the wavy line has the same meanings as defined above, in the presence of a base selected from an alkyl lithium, an alkali metal alkoxide, an alkali metal amide, an alkali metal hydride, or an alkali metal hydroxide, and optionally deprotecting;
3. a process for producing retinol, which comprises reacting the disulfone compound of formula (1): 
xe2x80x83wherein Ar, R1 and the wavy line have the same meaning as defined above, with a base selected from an alkali metal alkoxide, an alkali metal amide, an alkali metal hydride, or an alkali metal hydroxide, and optionally deprotecting;
4. an allylsulfone compound of formula (2): 
xe2x80x83wherein Ar and the wavy line have the same meanings as defined above;
5. a process for producing an allylsulfone compound of formula (2) as defined above, which comprises reacting the sulfone compound of formula (4): 
xe2x80x83wherein R, Ar and the wavy line have the same meanings as defined above, with an arylsulfinate of formula (5):
ArSO2Mxe2x80x83xe2x80x83(5)
xe2x80x83wherein Ar has the same meaning as defined above in connection with formula (1), and M denotes an alkali metal, in the presence of a palladium catalyst; and
6. a process for producing a sulfone of formula (4) as defined above, which comprises reacting a sulfone of formula (6): 
xe2x80x83wherein Ar has the same meaning as defined above, with an allyl halide compound of formula (3): 
xe2x80x83wherein X, R and the wavy line have the same meanings as defined above, in the presence of a base selected from an alkyl lithium, an alkali metal alkoxide, an alkali metal amide, or an alkali metal hydride.